Autophagy and Its Comprehensive Impact on ALS

ABSTRACT

Autophagy is a degradative modality that involves intracellular elimination of proteins and organelles by lysosomes. It is a conservative process and plays a crucial role in cell growth and development, and keeping cellular homeostasis especially under stress-induced situations. Recently, increasing evidence suggests that autophagic alternations may contribute to amyotrophic lateral sclerosis (ALS) as one of initial factors. LC3-II and p62 are found increased in spinal cord of both ALS patients and experimental models, indicating overwhelming autophagic level. But the aggregation of ALS-associated proteins, including SOD1 and TDP-43 suggest possible insufficiency of autophagy induction. Besides, augment autophagic level through genetic pathway or rapamycin leads to paradoxical results in different neurodegenerative diseases models. So, it remains controversial about autophagic effects on ALS progress. In this review, we will depict a comprehensive role that autophagy plays in ALS and focus on the influence of impaired autophagic flux and excessive autophagic vacuoles (AVs) that may aggregate ALS development. And we will discuss the potential therapeutic targets through modulating autophagic level to treat this disease.

KEYWORDS: :

• amyotrophic lateral sclerosis
• autophagic flux
• autophagy
• SOD1
• TDP-43

ACKNOWLEDGMENTS

This work was supported by grant 2011CB510000 from the Major State Basic Research Development Program of China (973 Program) (to Dr. Bei-sha Tang), grant 2006AA02A408 from the National “863” High-Tech Research and Development Program of China (to Dr. Bei-sha Tang), grants 30570638, 30770735, and 30971035 from the National Natural Science Foundation of China (to Dr. Bei-sha Tang), and grant 30900469 from the National Natural Science Foundation of China (to Dr. Ji-feng Guo).